To evaluate the efficacy of the dose level/regimen(s) of RAD001recommended from the phase I with HT therapy. This will bebased on the evaluation of overall response rate according toRECIST [Post-Text Supplement 1].
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the efficacy of the dose level/regimen(s) of RAD001
recommended from the phase I with HT therapy. This will be
based on the evaluation of overall response rate according to
RECIST [Post-Text Supplement 1].
Secondary outcome
To evaluate Progression Free Survival (PFS)
To evaluate the Time To Progression (TTP)
To evaluate overall survival (OS)
To describe the safety profile of the studied recommended dose
level/regimen(s)
Background summary
Weekly paclitaxel in combination with trastuzumab has been studied
in HER2-positive patients with previously treated, as well as previously
untreated metastatic breast cancer, and has demonstrated response
rates between 56% and 81% with a low incidence of grade 3-4
toxicities.
The optimal duration of trastuzumab therapy is currently not known
but there is emerging evidence that suggests that continuing
trastuzumab treatment even after progression of the disease, while
changing the chemotherapy partner, may produce clinical benefit.
Preclinical rationale is established for the combination of an mTOR
inhibitor with trastuzumab; loss of PTEN predicts resistance to
trastuzumab.
Evidence that inhibition of the mTOR pathway can enhance efficacy of
paclitaxel has been shown with the RAD001 in preclinical models.
RAD001 (everolimus), a derivative of rapamycin, is a signal
transduction inhibitor that acts by selectively inhibiting mTOR
(mammalian target of rapamycin), a serine-threonine kinase
implicated in the P13/AKT pathway and essential for the regulation of
cell growth and proliferation in many cell systems.
Pre-clinical investigations have demonstrated that RAD001 is a potent
inhibitor of the proliferation of a range of human tumor cell lines in vitro
and inhibits tumor growth in vivo in a range of animal models.
RAD001 is currently being evaluated in clinical trials both as a
monotherapy and in combination with other anti-cancer agents. Early
results show that RAD001 is generally well tolerated and that single
agent therapy may induce prolonged disease stabilization and even
tumor regressions in a subset of patients.
Study objective
To evaluate the efficacy of the dose level/regimen(s) of RAD001
recommended from the phase I with HT therapy. This will be
based on the evaluation of overall response rate according to
RECIST [Post-Text Supplement 1].
Study design
In phase II a 10 mg daily RAD001 continuous regimen will be used. (Only one arm
will be used).
Treatment will be repeated every 28 days for at least 6 cycles unless
there is evidence of progression or occurrence of unacceptable
toxicities. Following completion of chemotherapy (or early
discontinuation of chemotherapy), patients may continue to receive
RAD001 on a daily or weekly basis along with trastuzumab or alone (if
trastuzumab is discontinued early for toxicity), until progressive
disease or unacceptable toxicity occurs.
Intervention
Patients will be instructed to use RAD001 10 mg daily dose. Tablets contain
2,5 / 5 / 10 mg each.
Study burden and risks
After the screeningsperiod patients have to visit the hospital once every week
during the first 6 cycles. (Core phase).
After 6 cycles the extension phase of the study starts for patients who have
not yet progressive disease. During the extension phase patients have to visit
the hospital on day 1, 8, and 15 of each cycle (cycle is 21 days).
Tumor evaluation will be done every 8 weeks during the core phase and every 9
weeks during the extension phase.
Use of RAD001 might cause side effects.
Raapopseweg 1
6824 DP Arnhem
NL
Raapopseweg 1
6824 DP Arnhem
NL
Listed location countries
Age
Inclusion criteria
* Patients with histologically confirmed diagnosis of metastatic breast cancer demonstrating HER2-overexpression.
* Patients must have progressive disease on therapy or within 3 months of the last trastuzumab dose for advanced disease OR recurrence within 12 months of completing trastuzumab-based therapy as (neo) adjuvant therapy.
* Patients may have received adjuvant chemotherapy and one or more prior chemotherapies for advanced disease.
Exclusion criteria
* Patients receiving endocrine therapy for breast cancer < 2 weeks prior to study treatment start (endocrine therapy must have either failed in patients with hormone receptor positive disease or patients must be considered unsuitable for endocrine therapy).
* Patients who received chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to study treatment start or patients who have received lapatinib < 2 weeks prior to study treatment start.
* Patients who have previously received mTOR inhibitors.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-001596-37-NL |
| ClinicalTrials.gov | NCT00426556 |
| CCMO | NL25462.068.08 |